1. Field of the Invention
The present invention relates to 3,6-disubstituted pyridazine derivatives and, more particularly, to 3,6-disubstituted pyridazine derivatives which have platelet agglutination inhibitory action and, hence, are useful as a preventive medicine or a therapeutic medicine for a cerebrovascular disorder such as cerebral thrombosis and cerebral embolism, an ischemic heart disease such as myocardial infarction, and a circulation disorder such as a peripheral circulation disorder. The present invention also relates to optical antipodes of such 3,6-disubstituted pyridazine derivatives and pharmaceutically acceptable acid-addition salts thereof.
2. Description of the Prior Art
Most cerebrovascular disorders such as cerebral thrombosis and cerebral embolism, ischemic heart diseases such as myocardial infarction, and circulation disorders such as a peripheral circulation disorder are caused by a thrombus which is produced in a blood vessel and which occludes the blood vessel. Such a thrombus is produced mainly because platelets agglutinate in the earlier stage of the formation of the thrombus.
As compounds having a platelet agglutination inhibitory action, various 4-phenylphthalazine derivatives are conventionally known. For example, Japanese Patent Laid-Open Nos. 53659/1981, 53660/1981 and 48972/1982 disclose 1-anylino-4-phenylphthalazine derivatives, and Japanese Patent Laid-Open Nos. 218377/1985 and 243074/1985 disclose the compounds represented by the following general formulas (II) and (III), respectively, as compounds having a strong platelet agglutination inhibitory action in vitro: ##STR4##
These compounds, however, show almost no platelet agglutination inhibitory action whey they are administered orally, or the platelet agglutination inhibitory action in vivo cannot be said to be satisfactory.
British Patent No. 1303016, Journal of Medicinal Chemistry, 12,555 (1969), etc. disclose 1-amino-4-phenylphthalazine derivatives represented by the following general formula (IV): ##STR5## wherein R.sup.5 represents a hydrogen atom or a chlorine atom, R.sup.6 represents an alkyl group having 1 to 3 carbon atoms, --(CH.sub.2).sub.y N(CH.sub.3).sub.2, wherein y represents 2 or 3, a cyclohexyl group, or ##STR6## wherein x represents 1 or 2.
However, the compounds concretely disclosed have a restricted structure, and only an anti-inflammatory action and an anti-rheumatoid action are described as the pharmaceutical effects thereof.
As phthalazine derivatives having a non-substituted imidazole group at the fourth position, Japanese Patent Laid-Open Nos. 129180/1990, 129181/1990, 129182/1990 and 129183/1990 disclose compounds represented by the following general formulas (V) to (VIII), respectively: ##STR7## wherein E represents --NH--, --O-- or --S--, and R.sup.7 represents a straight-chain or branched-chain alkyl group having ! to 18 carbon atoms, a straight-chain or branched-chain alkyl group having 2 to 4 carbon atoms containing a hydroxyl group, an allyl group, a 3-methoxypropyl group, a tetrahydrofurfuryl group, a furfuryl group, a benzyl group which may be substituted by a chlorine atom or an alkyl group, or a phenyl group which may be substituted by a phenethyl group, a pyridylmethyl group or a chlorine atom, provided that when E is --NH--, R.sup.7 is not a substituted or non-substituted phenyl group; ##STR8## wherein R.sup.8 represents a lower alkoxyphenyl group, an allyloxyphenyl group, a pyridylmethyloxyphenyl group, a furyl group which may have a substituent, a thienyl group which may have a substituent, or a naphthyl group which may have a substituent; ##STR9## wherein R.sup.9 which may be the same or different from each other represents a hydroxyl group, a lower alkyl group, a methoxy group, an acetylamino group, a halogen atom, a methylthio group or an ethoxycarbonylvinyl group, and l represents an integer of 0 to 3; and ##STR10## wherein R.sup.10 represents a hydrogen atom, a lower alkyl group, R.sup.11 which may be the same or different from each other represents a hydroxyl group, an alkyl group having 1 to 5 carbon atoms, a lower alkoxy group, an acylamino group, a halogen atom, a cyano group, a nitro group, an anmino group, a carboxyl group, a lower alkoxycarbonyl group, a lower alkylcarbonyl group or an alkylthio group, and l represents an integer of 0 to 3.
As a phthalazine derivative having a non-substituted pyridyl group at the fourth position, Japanese Patent Laid-Open No. 106873/1991 discloses a compound represented by the following general formulas (IX): ##STR11## wherein R.sup.12 represents a hydrogen atom or a methoxy group, and R.sup.13 represents --NR.sup.14 R.sup.15, wherein R.sup.14 represents an alkyl group, a phenyl group which may be substituted by a halogen atom or a cyano group, or a pyrimidinyl group which may have a substituent, and R.sup.15 represents a hydrogen atom or a lower alkyl group, or R.sup.14 and R.sup.15 may combine to form a piperidino group, a piperazino group, a morpholino group or an imidazolyl group.